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Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 163 records · Page 9Linked to original sources

Suppression of laser-induced choroidal neovascularization by oral tranilast in the rat.

PURPOSE: To determine whether tranilast administered to pigmented rats inhibits formation of choroidal neovascularization induced by diode-laser photocoagulation. METHODS: Female Brown Norway rats were used. On day 0, choroidal neovascularization was induced by diode-laser photocoagulation, using a setting of 75 microm spot size, 0.1 second's duration, and 100 mW intensity. Tranilast (200 or 600 mg/kg per day) was administered orally twice daily for 14 days. Indomethacin (1 and 5 mg/kg per day) was administered orally once a day for 14 days. Choroidal neovascularization was evaluated on days 7 and 14 by fundus photography and fluorescein angiography. Late-phase fluorescein angiography was scored according to four grades. The animals were killed on day 14, and the lesions were evaluated histologically. RESULTS: In the vehicle-treated group, 34 of 35 burns (97%) showed fluorescein staining and late leakage on day 14. Choroidal neovascularization was identified by light microscopy in all the lesions that showed fluorescein staining and late leakage. The score of fluorescein staining was reduced in rats given 200 mg/kg per day or 600 mg/kg per day (P < 0.01) of tranilast. The thickness of the laser-induced lesions was reduced in a dose-dependent manner by tranilast, a significant difference was observed with 600 mg/kg per day (P < 0.05). Oral indomethacin treatment did not reduce fluorescein staining on day 14. CONCLUSIONS: Tranilast inhibits the development of choroidal neovascularization in this experimental model.

Administration, Oral↗

A possible role for p16INK4 in neuronal cell death after retinal ischemia-reperfusion injury.

PURPOSE: To study whether cell type-specific death occurs in retinal ischemia-reperfusion injury and the possible roles of p16INK4 in the determination of cell death. METHODS: Retinal ischemia-reperfusion injury was induced in rats by a ligation method. After 1 hour of ischemia and a time of reperfusion that varied, rat eyes were enucleated. Cell death in the retina was studied by the TdT-dUTP terminal nick-end labeling method and propidium iodide (PI) staining. Electron microscopic observation of the retina was also performed. Immunohistochemical studies using antibodies against syntaxin and calbindin were performed to detect amacrine cells and horizontal cells, respectively, and immunohistochemical studies using an antibody against p16INK4 were performed to study whether this cell cycle-related protein was expressed in dying cells. RESULTS: Most of the calbindin-positive horizontal cells in the outer aspect of the inner nuclear layer (INL) showed morphologic features of necrosis. In contrast, syntaxin-positive amacrine cells in the inner aspect of the INL showed features of apoptosis. Of 320 calbindin-positive horizontal cells, only 11 (3.4%) showed positive PI staining. Those calbindin-positive, horizontal cells were p16INK4 positive. In contrast, 746 of 910 (82.0%) syntaxin-positive amacrine cells showed condensed PI staining, and none were p16INK4 positive. CONCLUSIONS: Expression of p16INK4 may regulate the fate of retinal neurons in ischemia-reperfusion injury, and cell type-specific death thus occurs in the retina after such injury.

Animals↗

Expression of tissue factor in hepatic ischemic-reperfusion injury of the rat.

BACKGROUND: Tissue factor (TF) is a membranous protein normally present on the surface of the fibroblasts and smooth muscle cells of vessels. TF is an initiation factor for blood coagulation, and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. We studied the significance of TF expression in warm ischemic-reperfusion injury of the liver using a rat model. METHODS: Following laparotomy of Lewis rats, the branches of the hepatic artery and portal vein leading to the median, left, and caudate lobes of the liver were clamped for 2 hr. The liver was reperfused after 120 min of ischemia. Rats were killed at 0, 1, 3, 5, 8, and 12 hr after reperfusion, and liver tissues were harvested. TF activity was measured by the chromophilic substrate S-2222. TF expression was studied by immunohistochemical staining with the monoclonal antibody HTF-K108. RESULTS: TF activity in the blood showed a peak at 3 hr after reperfusion (8.9+/-0.5 U/L), then decreased and returned to the normal level by 12 hr (0.9+/-0.3 U/L). TF activity in ischemic liver tissue increased gradually over 12 hr after reperfusion (1223+/-275 U/g dry weight before ischemia and 2545+/-284 U/g weight at 12 hr after reperfusion). Histologically spotty necroses were observed in the liver tissue 5 hr after reperfusion. The necrotic area extended and encompassed almost all of the ischemic liver by 12 hr after reperfusion. Histochemically, TF staining was negative on the hepatocytes and slightly positive on sinusoid cells of the normal liver. On the other hand, TF was strongly stained, especially on the hypertrophic monocytic cells accumulating at the site of the necrosis, but staining was not evident on the necrotic hepatocytes. A slight degree of TF staining was observed on the alveolar epithelium of the lung, irrespective of liver ischemia and reperfusion. CONCLUSION: These results demonstrate that TF plays an important role in the development of the hepatic ischemic-reperfusion injury, and the subsequent microcirculatory incompetence might cause the formation of microthrombus and the development of necrosis.

Alanine Transaminase↗

The expression and localization of fibroblast growth factor-1 (FGF-1) and FGF receptor-1 (FGFR-1) in human breast cancer.

Fibroblast growth factor-1 (FGF-1) is an inducer of angiogenesis, the growth of new blood vessels. The expression and localization of FGF-1 (acidic FGF) and FGF receptor (FGFR)-1 in mammary tissues from patients with breast cancer was investigated using Western blot analysis and immunohistochemistry. The affinity-purified FGF-1 antibody which did not have cross-reactivity to FGF-2 (basic FGF) was used in this study. Western blot analysis demonstrated the presence of FGF-1 protein in all of the samples from breast cancer, but not benign tumors such as mastopathy and fibroadenoma. To assess the localization of FGF-1 in cancer tissues, immunostaining with specific antibody was performed. All samples from breast cancer displayed significantly intense staining with FGF-1 antibody. The extent and intensity of immunoreactive FGF-1 polypeptides in cancer cells was statistically much greater than those of cells from fibroadenoma or mastopathy. Control immunostaining with normal rabbit serum or anti-FGF-1 antibody adsorbed with the recombinant FGF-1 polypeptide was completely negative. In contrast to FGF-1, Western blot analysis demonstrated the presence of FGFR-1 protein in all of the samples from breast cancer and benign tumors. By immunohistochemical analysis, the enhanced expression of FGFR-1 was observed in breast cancer cells. Benign tumor cells or interstitial cells displayed a faint expression of FGFR-1. These results demonstrated that breast cancer cells not only generated FGF-1, but also expressed FGFR-1, and FGF-1 might play a role in the proliferation of breast cancer cells not only by paracrine but also by autocrine mechanism.

Adult↗

Ocular hypotension induced by intravitreally injected C-type natriuretic peptide.

The purpose of the study is to determine if intravitreal injection of c-type natriuretic peptide (CNP) affects intraocular pressure (IOP), aqueous humor dynamics and guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the aqueous humor of the rabbit eye. Also we investigated whether CNP-like immunoreactivities (CNP-LI) were present in porcine aqueous humor and whether CNP-LI were detected in rabbit and porcine ciliary body. The IOP was measured after intravitreal injection of 2 pmol approximately 20 nmol CNP into rabbit eyes. Aqueous humor dynamics (aqueous humor flow, outflow facility, and uveoscleral outflow) and cGMP concentration in the aqueous humor were determined at approximately 6 hr after CNP injection. The CNP concentration in aqueous was measured by radioimmunoassay in porcine eye, and CNP-LI were detected with a monoclonal antibody in porcine and rabbit eyes. Intravitreally injected CNP caused IOP reduction in a dose-dependent manner (P<0.0001) and the maximum effect was observed at 4 approximately 6 hr. CNP increased total outflow facility by approximately 35%, but did not affect aqueous humor flow or uveoscleral outflow. The cGMP concentration in the aqueous of CNP-treated eyes was about 4- to 14-fold higher than that in the contralateral untreated eyes. CNP concentration in aqueous was about 2-fold higher than that in plasma, and CNP-LI were found in non-pigmented epithelium of the ciliary body of both rabbit and porcine eyes. CNP may play an important role in the regulation of IOP.

Animals↗

Dynamic changes in intracapillary hemoglobin oxygenation in human skin following various temperature changes.

To evaluate microvascular regulation in human skin, changes in intracapillary hemoglobin oxygen saturation (HbO2) were studied in human finger skin following an abrupt change in local ambient temperature. In the first series of experiments, we assessed the heterogeneity of HbO2 in the skin by using a 2-D scanning system and a rapid micro-lightguide spectrophotometer at each of two near-normal skin temperatures. The data showed that heterogeneous oxygenation exists in human skin even at near-normal temperatures (although the pattern is different at different skin temperatures). In a second series of experiments, the performance of the microcirculation of the skin was continuously examined in a selected area with initially different oxygenation levels during an abrupt change in local ambient temperature (5, 15, 25, 35, and 45 degrees C). At very low (5 degrees C) or very high (45 degrees C) temperatures, oxygenation in tissues within the low HbO2 area increased greatly, but there was no such change within the high HbO2 area. Our data indicate that different types of capillary supply units exist in human skin (indicated by the initially different oxygenation levels). These different capillary supply units may operate to produce a local redistribution of flow between the various capillary supply units. This effect may be initiated by heat sensors and oxygen sensors when temperature of the skin is varied.

Adult↗

Successful surgical treatment of an Edwards type IIIB right aortic arch aneurysm: report of a case.

A true aneurysm of the right aortic arch which accompanies various branching characteristics is very rare. We report herein the successful surgical treatment of an elderly patient found to have an Edwards type IIIB right aortic arch aneurysm encircling and compressing the trachea. The complete right aortic arch and right subclavian artery were reconstructed through the inside of the aneurysm using selective cerebral perfusion. The patient recovered well, with no residual neurologic deficit and with resolution of the dyspnoic attacks he had suffered preoperatively.

Aortic Aneurysm, Thoracic↗

[Pulmonary artery sling with tracheal stenosis--primary repair in infancy].

Between 1984 and 1996 five infants underwent surgical repair of pulmonary artery sling associated with severe congenital tracheal stenosis. All infants had symptoms of severe respiratory distress and three of them required ventilator support preoperatively ages ranged from 2 to 11 months (mean age 6 months). Complete tracheal rings were present in all patients as an associated lesion and right upper lobe tracheal bronchus in 3 patients. The length of tracheal stenosis ranged from 18 to 45 mm (median 40 mm). Three had associated intracardiac anomalies (Scimitar syndrome (1), VSD (1), double-outlet right ventricle with VSD (1), double-outlet right ventricle with pulmonary hypertension (1)). Surgical intervention was carried out through a right thoracotomy (1) or median sternotomy (4). Cardiopulmonary bypass (CPB) was used in 3 patients and extracorporeal membrane oxgenator (ECMO). In 1. All infants had reimplantation of the left pulmonary artery into the main pulmonary artery left anterior to the trachea. Four patients underwent simultaneous tracheoplasty using costal cartilage grafts and one had complete resection of obstructed trachea between the right upper lobe tracheal bronchus and carina. The length of resected trachea was about 30% of the entire length of the trachea. Three infants underwent simultaneous intracardiac repair. There was no hospital death. All were weaned from ventilatory support and extubated on 1 to 16 months (mean 4, 5 months) postoperatively. AS an additional procedure, aortopexy, removal of granulation tissue or balloon dilatation of the trachea were carried out in one patient each following tracheoplasty using cartilage grafts. There was one late death at 1 year postoperatively. Three of 4 survivors are doing well with no stridor. We adonostridor. We adovocate 1) early aggressive primary repair of pulmonary artery sling with tracheal stenosis, 2) concomitant repair of tracheal lesion and intracardiac anomalies whenever possible, 3) application of CPB or ECMO to avoid cumbersome intubation technique, and 4) utmost effort to perform tracheal resection and end-to-end anastomosis.

Anastomosis, Surgical↗

Determinants of bone loss in a rural Japanese community: the Taiji Study.

The objective of this study was to assess the rate of bone loss and characterize its determinants, among the inhabitants of Taiji, a rural Japanese community. A cohort of 2261 inhabitants aged 40-79 years was established using resident registration in 1992. Fifty men and 50 women in each of four age strata between 40 and 79 years were randomly selected and completed a self-administered risk factor questionnaire. Baseline bone density of lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry in 1993. BMD was measured again on the same participants in 1996. The rates of change of lumbar spine BMD in men in their 40s, 50s, 60s and 70s were 0.20%, 0.34%, 0.43% and 0.28% respectively. Rates in women were -0.35%, -1.02%, -0.10% and -0.20% respectively. At the femoral neck, rates of change in BMD among men in their 40s, 50s, 60s and 70s were 0.09%, -0.07%, 0.34% and 0.31% respectively. Femoral neck rates of change among women were -0.55%, 0.02%, 0.49% and -0.25% respectively. The rate of change of lumbar spine BMD was -0.24% in premenopausal women with regular periods, -1.99% in premenopausal women with irregular periods and -0.33% in postmenopausal women. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline weight and height were statistically significant predictors of bone loss rate. These data provide estimates of the rate of bone loss among Japanese men and women aged 40-79 years. They suggest that body build and menstrual function in women are important determinants of bone loss.

Adult↗

Comparative study of event-related potentials and positron emission tomography activation during a paired-associate memory paradigm.

Event-related potentials (ERP) and regional cerebral blood flow (rCBF) activation using 15O-labeled water associated with retrieval and retention of episodic memory were studied during a visual paired-association task with delayed response in eight healthy subjects. In both studies, the subjects memorized four pairs of figures during the learning period. They were presented with each cue (S1) and asked to judge whether the following figure (S2) formed one of the memorized pairs. In an attempt to identify brain activity related to memory function, a choice reaction task with delay was used as a behavioral control. The ERP study showed a posterior positive component in the difference waveform, which was obtained by subtracting responses in the choice reaction task from those in the paired association task, between 300 and 850 ms after S1 presentation. It was maximal at the parietal midline electrode and distributed predominantly over the left posterior quadrant of the scalp. The rCBF activation study showed a greater increase in rCBF in the right dorsolateral prefrontal cortex (Brodmann's area 46), left inferior frontal cortex (Brodmann's area 44/45), left thalamus, and bilateral cerebellar hemisphere during the paired association task as compared to the choice reaction task, which suggests a possible involvement of cerebello-thalamo-cortical circuit in the memory processing. Additionally, it is suggested that the scalp distribution of the ERP component may not necessarily represent regional cortical activation below the electrodes where such a component is observed and could indirectly represent activation in remote areas such as subcortical regions. It seems that ERP and rCBF activation may provide information about different aspects of higher brain function.

Adolescent↗

Development of extrahepatic arterial blood supply to the liver during hepatic arterial infusion chemotherapy.

The aim of this study was to evaluate the correlation of development of the collateral circulation to the liver during hepatic arterial infusion chemotherapy (HAIC) with the presence of hepatic tumours adjacent to the hepatic surface, and with pretreatment occlusion of aberrant hepatic arteries. In 102 patients with unresectable malignant hepatic tumours treated with HAIC using an implantable port system, development of collaterals to the liver was assessed with CT arteriography using the implantable port and pre- and postoperative angiography. Aberrant hepatic arteries, if present, were occluded prior to treatment for hepatic arterial redistribution. Collaterals to the liver were seen in 29 patients, who had 35 areas with collateral perfusion: 22 areas were in the right posterosuperior area, 6 in the left peripheral area and 7 in the right or left lobar area. Collaterals were revealed more frequently in patients with hepatic tumours adjacent to the hepatic surface than in those without hepatic tumours in peripheral areas in the liver (p < 0.0001). In addition, collaterals developed more frequently in patients with an aberrant hepatic arterial anatomy compared with those with conventional anatomy (p = 0.0007). Our results indicated that patients with hepatic tumours adjacent to the hepatic surface and with pretreatment occlusion of aberrant hepatic arteries had the potential to develop collaterals to the liver during HAIC.

Adult↗

Transcortical sensory aphasia following left frontal infarction.

Two right-handed patients who exhibited language disability after left frontal infarction are described. The patients spoke fluently and exhibited excellent repetition ability from the onset of infarction without exhibiting any oral apraxia, but had deficits in auditory comprehension, naming, reading and writing. In both patients, brain magnetic resonance imaging (MRI) revealed infarction in the left inferior frontal gyrus, the middle frontal gyrus and the anterior part of the lower precentral gyrus. Single photon emission computed tomography (SPECT) revealed decreased blood flow in the same regions as those shown to be infarcted by MRI. The MRI and SPECT findings and the symptoms of these patients suggest that left frontal lesions that encompass Broca's area produce fluent aphasia if the posterior part of the left precentral gyrus or motor cortex remains intact and that lesions anterior to Broca's area and the middle frontal gyrus produce a deficit in auditory comprehension of single words as well as sentences.

Aphasia, Wernicke↗

Expression of Fas antigen on helper T lymphocytes in Vogt-Koyanagi-Harada disease.

BACKGROUND: Our purpose was to analyze the expression of Fas antigen on CD4+ lymphocytes in the aqueous humor (AH) and cerebrospinal fluid (CSF) of patients with Vogt-Koyanagi-Harada disease (VKH). METHODS: Using three-color flow cytometry, we assessed T-lymphocyte subsets stained with fluorescence-conjugated anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies in AH, CSF and peripheral blood (PB) from 8 patients with active VKH. RESULTS: CD3+ T cells constituted the majority of lymphocytes in AH and CSF, in contrast to with PB. The percentages of CD4+ lymphocytes in uveitic AH and CSF were significantly higher than that in PB (P < 0.01). Activated CD4+ and CD8+ cells were significantly more frequent in AH than in CSF and PB (P < 0.01). Although the percentages of CD45RA+ cells within CD4+ cells in AH and CSF were extremely low compared with those in PB, the proportions of CD29+ and CD45RO+ (memory) cells within CD4+ were much higher than those in PB (P < 0.01). Fas antigen was also highly expressed on such CD4+ cells in AH, as in other uveitis patients and on such cells in CSF. Moreover, the percentages of Fas+ and memory cells in AH were significantly higher than those in CSF. CONCLUSIONS: The majority of CD4+ lymphocytes in AH and CSF from patients with active VKH were activated memory cells, on which Fas antigen was also highly expressed. Although this Fas expression may not be an apoptosis-related phenomenon, accumulation of Fas+ memory T lymphocytes in AH and CSF probably reflects the immunopathologic mechanism of VKH.

Adult↗

Growth of the subclavian artery and the anastomosis in Blalock-Taussig shunt: absorbable versus nonabsorbable suture.

BACKGROUND: We evaluated the growth of Blalock-Taussig shunts placed with absorbable suture by cineangiographic findings and long-term results and compared them with those in an earlier group of patients in whom we used nonabsorbable suture. METHODS: Eighty-one patients had postoperative cineangiography 1 year or more after a Blalock-Taussig shunt procedure. From September 1985 to December 1994, 40 patients (group I) underwent a Blalock-Taussig shunt procedure with the use of absorbable polydioxanone suture, and from January 1980 to August 1989, 41 (group II) underwent the same operation with nonabsorbable polypropylene suture. Cineangiograms were reviewed to assess shunt patency and growth of the subclavian arteries and the subclavian artery-pulmonary artery anastomoses. RESULTS: At the Blalock-Taussig shunt operation, mean outer diameters of the subclavian artery and the anastomosis in group I were 3.8 +/- 0.1 mm and 4.1 +/- 0.1 mm, respectively and 3.9 +/- 0.1 mm and 4.0 +/- 0.1 mm in group II. The mean inner diameters of the subclavian artery and the anastomosis measured in postoperative cineangiograms were 7.9 +/- 0.5 mm and 4.6 +/- 0.2 mm, respectively in group I and 6.6 +/- 0.4 mm and 3.1 +/- 0.2 mm in group II. The diameters of both the subclavian artery (p < 0.05) and the anastomosis (p < 0.001) were significantly greater in group I than in group II. Five years after operation, 71.1% +/- 7.4% of patients in group I and 54.8% +/- 8.0% in group II had good palliation. CONCLUSIONS: The use of absorbable polydioxanone suture has an advantage in terms of growth of the diameters of the subclavian artery and the anastomosis in a Blalock-Taussig shunt and may improve the long-term results after this shunt operation in infancy.

Absorption↗

Inhibition by tranilast of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF)-induced increase in vascular permeability in rats.

We studied the effects of tranilast, an anti-allergic and anti-proliferative drug in clinical use, on VEGF/VPF-induced vascular permeability in a rat air pouch model. A large increase in vascular permeability was induced by injection of 4 ml of a 100 ng/ml VEGF/VPF solution into the preformed air pouch. Over a 15-min period, tranilast inhibited the VEGF/VPF-induced vascular permeability in a dose-dependent manner. This result suggests that tranilast, which we recently found to inhibit VEGF/VPF-induced angiogenesis, could also improve VEGF/VPF-dependent increases in vascular permeability.

Animals↗